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Development and validation of serological markers for detecting recent exposure to Plasmodium vivax infection

View ORCID ProfileRhea J. Longley, Michael T. White, Eizo Takashima, Jessica Brewster, Masayuki Morita, Matthias Harbers, Leanne J. Robinson, Fumie Matsuura, Shih-Jung Zoe Liu, Connie S. N. Li-Wai-Suen, Wai-Hong Tham, Julie Healer, Christele Huon, Chetan E. Chitnis, Wang Nguitragool, Wuelton Monteiro, Carla Proietti, Denise L. Doolan, Xavier C. Ding, Iveth J. Gonzalez, James Kazura, Marcus Lacerda, Jetsumon Sattabongkot, Takafumi Tsuboi, Ivo Mueller
doi: https://doi.org/10.1101/481168
Rhea J. Longley
1Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
2Department of Medical Biology, University of Melbourne, Melbourne, Australia.
3Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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  • ORCID record for Rhea J. Longley
Michael T. White
4Malaria Parasites & Hosts Unit, Department of Parasites & Insect Vectors, Institut Pasteur, Paris, France.
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Eizo Takashima
5Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan.
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Jessica Brewster
1Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
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Masayuki Morita
5Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan.
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Matthias Harbers
6CellFree Sciences Co., Ltd., Yokohama, Japan.
18RIKEN Center for Integrated Medical Sciences (IMS), Yokohama, Japan.
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Leanne J. Robinson
1Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
2Department of Medical Biology, University of Melbourne, Melbourne, Australia.
7Burnet Institute, Melbourne, Australia.
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Fumie Matsuura
6CellFree Sciences Co., Ltd., Yokohama, Japan.
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Shih-Jung Zoe Liu
1Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
2Department of Medical Biology, University of Melbourne, Melbourne, Australia.
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Connie S. N. Li-Wai-Suen
1Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
2Department of Medical Biology, University of Melbourne, Melbourne, Australia.
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Wai-Hong Tham
2Department of Medical Biology, University of Melbourne, Melbourne, Australia.
8Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
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Julie Healer
2Department of Medical Biology, University of Melbourne, Melbourne, Australia.
8Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
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Christele Huon
9Malaria Parasite Biology and Vaccines, Department of Parasites & Insect Vectors, Institut Pasteur, Paris, France.
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Chetan E. Chitnis
9Malaria Parasite Biology and Vaccines, Department of Parasites & Insect Vectors, Institut Pasteur, Paris, France.
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Wang Nguitragool
10Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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Wuelton Monteiro
11Fundacão de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil.
12Universidade do Estado do Amazonas, Manaus, Brazil.
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Carla Proietti
13Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
14QIMR Berghofer Medical Research Institute, Brisbane, Australia.
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Denise L. Doolan
13Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
14QIMR Berghofer Medical Research Institute, Brisbane, Australia.
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Xavier C. Ding
15Foundation for Innovative New Diagnostics, Geneva, Switzerland.
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Iveth J. Gonzalez
15Foundation for Innovative New Diagnostics, Geneva, Switzerland.
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James Kazura
16Center for Global Health and Diseases, Case Western Reserve University, Cleveland, United States.
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Marcus Lacerda
11Fundacão de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil.
17Instituto Leônicas & Maria Deane (Fiocruz), Manaus, Brazil.
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Jetsumon Sattabongkot
3Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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Takafumi Tsuboi
5Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan.
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Ivo Mueller
1Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
2Department of Medical Biology, University of Melbourne, Melbourne, Australia.
4Malaria Parasites & Hosts Unit, Department of Parasites & Insect Vectors, Institut Pasteur, Paris, France.
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  • For correspondence: mueller@wehi.edu.au
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Abstract

In order to accelerate towards malaria elimination, improved targeting of limited resources is essential. A major gap in our elimination toolkit for Plasmodium vivax malaria is the identification of individuals carrying arrested liver stages, called hypnozoites. These clinically silent but frequently relapsing hypnozoites are key to P. vivax persistence. Whilst hypnozoites cannot be directly detected, individuals who have had recent exposure to P. vivax and have not been treated are likely to harbor these parasites. By measuring IgG antibody responses to over 300 P. vivax proteins, a panel of serological markers capable of detecting exposure to P. vivax infections in the prior 9-month period was identified and validated. Using antibody responses to 8 P. vivax proteins, 80% sensitivity and specificity for detecting recent infections were achieved in three independent studies conducted in Thailand, Brazil and the Solomon Islands. As these individuals have a high likelihood of harboring hypnozoites, the suite of these 8 antibody responses can serve as biomarkers for the identification of individuals who should be targeted for treatment with liver-stage drugs such as primaquine and tafenoquine in mass drug administration programs aimed at controlling and eliminating P. vivax malaria.

One Sentence Summary The manuscript describes identification and validation of a novel panel of P. vivax proteins that can be used to detect recent exposure to P. vivax infections within the prior 9 months.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 30, 2018.
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Development and validation of serological markers for detecting recent exposure to Plasmodium vivax infection
Rhea J. Longley, Michael T. White, Eizo Takashima, Jessica Brewster, Masayuki Morita, Matthias Harbers, Leanne J. Robinson, Fumie Matsuura, Shih-Jung Zoe Liu, Connie S. N. Li-Wai-Suen, Wai-Hong Tham, Julie Healer, Christele Huon, Chetan E. Chitnis, Wang Nguitragool, Wuelton Monteiro, Carla Proietti, Denise L. Doolan, Xavier C. Ding, Iveth J. Gonzalez, James Kazura, Marcus Lacerda, Jetsumon Sattabongkot, Takafumi Tsuboi, Ivo Mueller
bioRxiv 481168; doi: https://doi.org/10.1101/481168
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Development and validation of serological markers for detecting recent exposure to Plasmodium vivax infection
Rhea J. Longley, Michael T. White, Eizo Takashima, Jessica Brewster, Masayuki Morita, Matthias Harbers, Leanne J. Robinson, Fumie Matsuura, Shih-Jung Zoe Liu, Connie S. N. Li-Wai-Suen, Wai-Hong Tham, Julie Healer, Christele Huon, Chetan E. Chitnis, Wang Nguitragool, Wuelton Monteiro, Carla Proietti, Denise L. Doolan, Xavier C. Ding, Iveth J. Gonzalez, James Kazura, Marcus Lacerda, Jetsumon Sattabongkot, Takafumi Tsuboi, Ivo Mueller
bioRxiv 481168; doi: https://doi.org/10.1101/481168

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